Quaternary alkyl aromatics

ABSTRACT

Quaternary alkylated aromatics prepared by alkylation of unsaturated bond using dialkylcopper lithium which are useful for control of insects.

United States Patent 91 Siddall [4 1 Apr." 17, 1973 54] QUATERNARY ALKYLAROMATICS 58 Field of Search ..260/476 R, 515 R 75 I t h B. dd P Alt,Cal'f. nven or J0 n 810 0 1 [56] References Cited [73] Assignee: ZoeconCorporation, Palo Alto, I

Cam UNITED STATES PATENTS 22 Filed: 2 1970 3,578,699 5/1971 Sorm et a]...424/308 PP 32,767 Primary ExaminerLorraine A. Weinberger AssistantExaminerR. S. Weissberg Related .Apphcauon Data Att0rneyDonald W.Erickson [63] Continuation-impart of Ser. No. 21,182, March 19, I

I970, abandoned. [57] I ABSTRACT v Quaternary alkylated aromaticsprepared by alkylat io'n 260/327 26O/34O'9 of unsaturated bond usingdialkylcopper lithium which 260/515 R, 260/592, 424/277, 424/278,424/308, 424/317, 424/331 Int. Cl. ..-..C07c 63/06, CO7C 69/78 areuseful for control of insects.

15 Claims, No Drawings 1 QUATERNARY ALKYL AROMATICS This is acontinuation-in-part of application Ser. No. 21,182, filed Mar 19, 1970,now abandoned.

The present invention relates to novel quaternary alkyl compounds of thefollowing formulas A, B and C and the use thereof and compositionsthereof for the control of insects.

Ha CH-z wherein,

R is alkyl, alkoxy, benzyloxy or hydroxy;

R is alkyl or benzyl;

each of R and R is hydrogen or lower alkyl, provided that at least one Rand R is lower alkyl;

R is l-I,I-l or 0x0 and the cycloethylene ketal or cycloethylenethioketal thereof;

R is 0x0 and the cycloethylene ketal or 'cycloethylene thioketalthereof; and each of R and R is lower alky.

The refers alkyl, as used herein, refers to an alkyl group, branched orstraight chain, having a chain length of one to six carbon atoms. Theterm lower alkyl, as used herein, reters to a straight chain alkyl groupof one to four carbon atoms. The term alkoxy, as used herein, refers toa straight or branched chain alkoxy group having a chain length of oneto six carbon atoms.

The compounds of the present invention are prepared according to thefollowing outlined syntheses wherein R, R and R are as defined above andR is alkyl or benzyl.

In the practice of the above-outlined syntheses, a compound of formula Iis oxidized using chromiun trioxide in acetic acid, or the like, toyield the corresponding .ketone (II) which is reacted with di (loweralkyl) copper lithium reagent to yield a mixture of compounds III andIV. The organo-copper reagent is prepared by the reaction of lower alkyllithium with a cuprous salt, such as cuprous iodide at low temperature.A compound of formula III or IV or mixture thereof is alk-ylated usingdi(lower alkyl)copper lithium to yield V, Compounds III and IV arehydrogenated to the respective compounds VI and VII by catalytichydrogenation using platinum oxide, or the like. The

' responding free acids are obtained (A; R is hydroxy).

The compounds of formula-A wherein R is alkyl are obtained by treatingthe acid (A;' Rvis hydroxy) with alkyl lithium. Prior.to"- carrying outthis reaction, the

A carbonyl (A; R? is oxo )is converted to the corresponding lowercycloalkylene ketal using the corresponding glycol in the presence ofacid catalyst and then, upon completion of the reaction, the ketalprotecting group isremoved by treatment with acid to regeneratethecarbonyl group. Alternatively, the carbonyl group is i reduced bytreatment with sodium borohydride in aqueous ethanol, the acid convertedto the keton- (A; R is alkyl).and the hydroxy then oxidized back to thecarbonyl using Jones reagent, maganese dioxide, chromi- I um trioxide,orthe like.

' The compounds of formula l are described by Slama,

Suchy and Sorm, The' Biological Bulletin 134, No. 1,

Science 162,582 (November 1, I968).

' l54;(February, 1968) and Suchy, Slama and Sorrn,

- The various esters of the present invention can be prepared bytransesterificationor by conversion of an the appropriate alcohol,affords the ester desired. I

The compounds of the present invention are useful I for the control ofinsects. The effectiveness of these compounds, is attributed to theirjuvenile hormone activity. They are applied using liquid or solidcarriers and preferably, me time so as to contact the immature insectduring the embryo or larvae stage of the insects life. The compounds offormula A are also effective against the adult female as achemosterilant. The control of insects can be broughtby such means ascontact of the compound with the insect by direct topical contact, vaporcontact, contact through ingestion, or transmittal from one insect toanother through physical contact. For example, topical application, asby spraying, of a compound of the present invention to an insect duringthe egg or larvae stage effectively inhibits the "passage of the insectto the next metamorphic stage. In

, order of 0.00l pg. to 5 pg. per insect. In the application of thecompounds, the'application can be such as to apply lower or higherdosages of the aforementioned range'based on such factors as theestimated insect population, environmental conditions, locus of theinsects and previous trials. .The compounds of the present invention areselectively active control agents for Hemipteran, the familyPyrrhocoridae. They are particularly effective against Pyrrhocorisapterus and members of the genus Dysdercus, such as Dysdercusintermediates. Carriers, such as mineral and vegetable oils, e.g.refined kerosene, xylene, toluene, cottonseed oil, sesamol, and thelike, and solid carrier s, such as silica, talc, resins, syntheticpolymers, can be used to dilute the active ingredient. Insect attractants or pheromones can also be includedJEmulsifying agents and wettingagents can be used in formulations of the compounds of the presentinvention to assist in application.

The following examples are provided to illustrate the preparation of thenovel compounds of the present invention and the practice of the presentinvention. Tem-v perature in degrees Centigrade.

EXAMPLE I (A) A mixture of s g. of methylp-(l,5-dimethylhexa-l,4-d'ienyl)benzoate, 1.5 molar equivalents ofchromium trioxide dissolved in 3 ml. of water and {10 ml. of acetic acidis stirred at room temperature for about 2 hours and then quenched withisopropyl alcohol. The reaction mixture is-then poured into water andextracted with ether. The combined ethereal extracts are washed withwater and brine, dried and' evaporated to yield methyl p-(l,5-dimethyl-3oxohexa-l ,4-dienyl)benzoate (II; R' is methyl) which is pu; rified bychromatography on silica. A

EXAMPLE 2 To a mixture of 1.3 g. of cuprous iodide and 50 ml. of

dry ether under nitrogen, cooled to ;lQ, is added 8 ml. of 1.65M methyllithium in ether. After negativeGiL.

man test (about l5 minutes), 0.5' g.-of methyl p -(1,5.-

dimethyl-3-oxohexa'l ,4-dienyl-)benzoate in ether is addedwhilemaintaining the I temperature at about l0. The reaction is worked upafter afout 30 minutes by pouring into saturated ammonium chloride andextracting with ether. The combined ethereal extracts are washed withsaturated ammonium chloride,:water arid brine, dried over sodium sulfateand evaporated to yield a mixture containing methyl p- 1,5,5-trimthyl-3-oxohexa-l-enyl)benzoate (III;R' R? methyl) and methyl p-( l ,l,5-trimethyl-3-oxohexa-4-enyl)benzoate (IV; R R methyl) which areseparated and purifled by chromatography. A

By repeating the process of this example using an equivalent amountofeach of ethyl lithium and n-butyl lithium in place of methyl lithium,there vis obtained methyl p-( l,5,5-trimethyl-3-oxoheptl -enyl )b'enzoate, methyl p-(1 ,5-dimethyl-l-ethylr3 -oxohex-4- enyl)benzoate,methyl p-(1,5,5-trimethyl-3 oxonon-lenyl) and methyl p-( l,5-dimethyl-l-n-butyl-3oxohex- 4-enyl)benzoate. Similarly, by using n-propyl lithium,there is obtained methyl p-(' l ,5,5-trimethyl-3- oxooct-lenyl)benzoateand methyl p-(l,5-dimethyl-l-nrpropyl- 3-oxohex-4-eny])benzoate.

EXAMPLE 3 A solution of 2 g. of methyl p-(1,5,5-trimethyl-3-oirohex-l-enyl)be'nzoate in. 20 ml. of ethanol 2.5hydrogenated at room temperature and atmospheric yl)benzoate,

1 oxohexyl )benzoate.

pressure in the presence ofZOO is mg. of platinum oxide with vigorousstirring until about 1.1 molar equivalents of hydrogen is absorbed. Thesystem is flushed with nitrogen andthe solution filtered through Celiteand the filtrate evaporated to yield methyl p-(1,5,5-trimethyl-3-oxohexyl)benzoate (VI; R R methyl).

By use of the foregoing process, each of the compounds obtained inExample 2 is hydrogenated to yield methyl methyl p-( l,5,5-trimethyl-3-oxoheptyl)benioate, methylp-(1,S-dimethyl-l-ethyl-3-oxohyxyl)-benzoate, methyl p( I ,5,5trimethyl-3-oxononyl)benzoate, methyl p-(l,S-dimethyl-l-n-butyl-3-oxohex- 1 methyl p-(l,5,5-trimethyl-3-oxooctyl)benzoate and methyl p-(1,5-dimethyl-l-n-propyl-3- EXAMPLE 4 A solution of 5 g. of methyl p-( l,5,5-trimethyl-3-oxohexyl)benzoate"(VI; F R methyl) in 100 ml. glacialacetic acid conta ning 5 ml. of ethane dithiol and 4 ml. of a saturatedsolution of hydrogen chloride in acetic acid is allowed to stand at roomtemperature for 4 hours. Water is added and resulting mixture extractedwith ethyl acetate. The combined extracts are washed with dilute aqueoussodium bicarbonate and water, dried over sodium sulfate and evaporatedto dryness to yield crude cycloethylene thioketal of methyl p-( 1,5,5-

trimethyl-3-oxohexyl)benzoate which can be purified by chromatography.Four grams of the crude thioketal in 100 ml. of ethanol (previouslydistilled over Raney nickel) and g. of degassed Raney nickel is heatedat reflux for about 6 hours. Then the metal is removed by filtration andwashed with hot ethanol and the filtrate concentrated by evaporation.The concentrate is taken up in chloroform, washed with dilute I-ICl,dilute sodium carbonate solution and water, dried over sodium sulfateand evaporated to yield methyl p-(l,5,5- trimethylhexyl)benzoate (VIII;R R methyl) which is purified by chromatography.

' By repeating the above process, each of the 3-oxo compounds isconverted into the corresponding cycloethylene thioketal which istreated with Raney nickel to yield methyl p-(1,1,5-trimethylhexyl)benzoate, methyl p'-(1,5,5-trimethylheptyl)benzoate, methyl p-( l,5-dimethyl-l-ethylhexyl)benzoate, methyl p.-( 1 ,5,5-trimethylnonyl)benzoate, methylp-( 1,5-dimethyll -n-butylhexyl )benzoate, methyl p-( l,5,S-trimethyloctyl)benzoate and methyl p-(l,S-dimethyl-l-n-propylhexyl)-benzoate.

EXAMPLES (A) A mixture of 3 g. of methyl p-( l ,5,5-trimethyl-3--oxohexyl)benzoate, 28 g. of -l,2-ethanediol, a few crystals ofp-toluenesulfonic acid monohydrate'and 100 ml. of dry benzene is heatedunder reflux for about 20 hours. After cooling, 0.2 ml. of pyridine isadded and then ether. The mixture is washed with water and brine and theorganic phase dried over sodium sulfate and evaporated under reducedpressure to yield methyl p-( l ,5,5-trimethyl-3,3-ethylenedioxyhexyl)benzoate.

p-(1,1,5-trimethyl-3-oxohexyl)benzoate,

Using the above process, the cycloethylene ketal of 0.2 g. of sodiumcarbonate and 6 ml. of water is stirred at about 30 for 3 hours. Themixture is diluted with water, neutralized and then extracted withether. The organic extracts are combined, washed with water, dried oversodium sulfate and evaporated to yield p-(l,5,5-trimethyl-3,3-ethylenedioxyhexyl)benzoic acid (A; R is hydroxyl,R is hydrogen, R is cycloethylenedioxy and R is methyl).

By use of the above process, each of the esters of Part A is hydrolyzedto the corresponding acid, that is,p-(1,1,5-trimethyl-3,3-ethylenedioxyhexyl)benzoic acid, tyl)ben2oicacid, p-( l ,S-dimethyll -ethyl-3,3-' ethylenedioxyhexyl)benzoic acid,p-(l,5,5-trimethyl- 3,3-ehtylenedioxynonyl)benzoic acid, p-( l,5-diemthyll-n-butyl-3,3-ethylenedioxyhexyl)benzoic acid, p-(l,5,5-trimethyl-3,3-ethylenedioxyoctyl)benzoic acid and p-(1,5-dimethyll -n-propyl-3,3-ethylenedioxyhex* yl)benzoic acid. A

-(C) To -a stirred solution of 2.5 g. of p-(l,5,5-trimethyl-3,3-ethylenedioxyhexyl)benzoic acid in 30 ml of dry ether isadded slowly, at 0, 25 ml. of one molar solution of methyl lithium inether. After about 3 hours at 20, the mixture is poured into iced INacetic acid ml.) with vigorous stirring. The ether layer is separated,combined with ethereal washings of the aqueous phase, dried with water,saturated potassium bicarbonate and then brine, dried over magnesiumsulfate and evaporated under reduced pressure to yield the correspondingmethyl ketone (A; R is methyl, R is hydrogen, R isc-ycloethylenedioxyand R is methyl).

By repeating the above process using other alkyl lithiums, such as ethyllithium in place of methyl lithium, the corresponding alkyl ketones areobtained,.e.g. the ethyl ketone (A, R is ethyl, R is hydrogen, R iscycloethylenedioxy and R is methyl).

(D) A mixture of l g. of the ethylene ketal of Part C, 40 ml. of aceticacid, 2.5 ml. of water and 0.5 ml. of concentrated surfuric acid isstirred at room temperature for about 2.5 hours. The mixture is thenpoured into water and extracted with ether. The combined etherealextracts are washed with water, saturated potassium bicarbonate solutionand brine. After drying EXAMPLE 6 Thionyl chloride (1 g.) is added understirring at room temperature to 0.5 g. of'p-(1,5,5-trimethyI-3-oxohexyl)-benzoic acid and the resulting mixtureheated with stirring and under dry conditions for about 15 minutes at50-70. Excess thionyl chloride is removed by evaporation to yield theacid chloride. Anhydrous ethanol (one or more equivalents) is added andthe resulting mixture heated under dry conditions at about 50 forevaporated to yield ethyl p-( l,5,5-trimethyl-3-oxohex ylbenzoate whichis purified by chromatography.

By using other alcohols in place of ethanol in the foregoing process,such as t-butanol, n-propanol,

p-( 1,5 ,5-trimethyl-3 ,3-ethylenedioxyhep- A I l()l5 minutes. Theexcess ethanol is formulas V and X 7 above.

'benzyl alcohol, n-hexanol, and the like, the corresponding t-butylester, n-propyl ester, benzyl ester, nhexyl'ester, and the like, areobtained.

Using the procedure of Example (8) and the process of this examplesother esters of formulas III, IV

and Vl-IX are prepared via the acid and acid halide thereof.

EXAMPLE 7 i 1 I The process of Example 5(B) is repeated usingeach of theesters of Example 4 to yield p-(l,5,5-trimethylhexyl)-benzoic acid,p-(1,l,5-trimethylhexy1)benzoic acid, .p-(l,S-dimethyl-1-ethylhexyl)benzoic acid, pl,5,5-trimethylheptyl)-benzoic acid, 'p-(1,5-dimethyll'-n -propylhexylacid, p-(l',5,5-trimethyloct)benzoic acid,p-( l ,S-dimethyl-l-n-butylhexyl)benzoic .acid and p-( l,5,5trimethylnonyl)benzoic acid.

The process of Example 5(C) is repeated usingeach of the above acids toyield the corresponding methyl ketone, that is, met'ryl 4-(1', 5',5'-trimethylhexyl)phenylketone ('A; R is methyl, R is hydrogen, R is H,Hand R is methyl), methyl 4-(1', 1', 5 -trimethylhexyl)phenyl ketone,methyl 4-(l,5'-dimethyl-l'- ethylhe'xyDphe'nyl ketone, methyl4-(1',5,5'- .trimethylheptyDphenyl ketone, methyl 4-(1,5- dimethyl-l-npropylhexyl)phenyl ketone, methyl 4- -dim ethyl-l'-nsbutylhexyl)phenylketone and methyl 4-(-.l ,5 5 '-trimethyln onyl)phenyl ketone.

Similarly, through the use of other alkyl lithiums in the process-ofExample 5(C), such as ethyl lithium, n-

EXAMPLE 8 The process of Example 2 is repeated with the exceptions ofusing methyl p-(l,l,5-trimethyl-3-oxohex-4- enyl)benzoate in place ofmethyl p-(l,5-dimethyl-3- oxohexa-l ,4-dienyl)benzoate and the reactionmixture is workedup six hours after addition of the methyl "benzoate tothe dimethyl lithium cuprate reagent to yield methyl p-(l,l,5,5-tetramethyl-3-oxohex- R methyl). The same compound is preparedusing methyl p-( 1,5,5-trimethyl- 3-oxohex-l-enyl)benz'oate as thestarting material. By this procedure, compounds of either formula III orIV are converted'into the compounds of formula V. By

, formation of the ethylene thioketal of the .compounds of formula Vvanddesulfurization 'thereof with Raney nickel according to the procedureof Example 4, the

corresponding compoundsof formula V are prepared.

Alkyl phenyl ketones are prepared from the esters of using the methodsof Examples 5 and Similarly, the procedure of Example 6 is utilized toprepare the acid halides and other esters of formulas V and x. 1

A'liquid concentrate is prepared of 50 parts methyl p-(l,5,5-trimethyl-3-oxohexyl)benzoate and 50 parts xylene. The concentrateis then diluted with water and/or other organic, liquid carrierstogether with wetting, dispersing or emulsifying agents, such as thealkyl or aralkyl sulfonates, sodium lauryl sulfate, alkylaryl polyetheralcohols, polyethylene oxides and other hexyl lithium, neopentyllithium, and the like, the corresponding ethyl phenyl ketone, n-hexylphenyl ketone, ne'opentyl phenyl ketone, and the like, are obtained.

surface-acetive agents. The concentration of methyl p-n propyleneglycol, cottonseed oil and toluene to contain from about 10-85 percentof the active ingredient. The

concentrates are also used for preparing solid formulations inwhich-case thevconcentrate, as is or diluted, is sprayed or mixed withsolid carriers, such as kaolin, bentonite, talc, diatomaceous earth,pumice, silicas, granular polyvinyl chloride or other carriers. Wettingagentsand other componets, such as paraffin wax or chlorinated paraffincan be added tocontrol the rate of vaporization. The amount of activeingredient in conuunction with solid carrier is normally about the sameas with liquid carriers.

EXAMPLE 9 Each of methyl p-( l,5,5-trirnethyl-3-oxohex-lenyl)- Ibenzoate, methyl p-( l ,l ,5-trimethyl-3-oxohex-4- enyl)benzoate, methylp-( 1,5,5-trimethyl 3-oxohept-I- enyl)benzoate and methylp-(1,5-dimethy1-1 ethyl 3 oxohex.-4-enyl)benzoa te is reacted withethane dithiol using the procedure of Example 4 to yieldthecorresponding cycloethylene thioketal.

EXAMPLE 1o By use of the procedure of Example 5A, each of the 3- oxocompounds of Example 2 is converted into the corresponding cycloethyleneketal, e.g.. methyl p- 1,5,5-trimethyl-3,3#ethylenedioxyhex-l- Ienyl)benzoate and" methyl p l ,l,5 -trir nethyl-3,3-ethylenedioxyhex-4-enyl)beni oate. Similarly, the oxo compounds offormula V'preparedas described in Example. 8 are converted intothecorr'es onding cycloethyleneketal and cyclolethylene thioke al usmgthe procedures of Example 5A and-Example 4.,- respectively.

What is claimed is: l r 1. A compound selected-fromthose of thefollowing formulas A, B and C: I

wherein, v I

R is alkoxy, benzyloxy or hydroxy;

R is alkyl or benzyl;

each of R and R is hydrogen or lower alkyl, provided that'at least oneof R and R is lower alkyl;

R is oxo; and each of R" and R is lower alkyl.

2. A compound of formula A according to claim 1 wherein R is hydrogen.

3. A compound according to claim 2 wherein R is alkoxy, and R is methylor ethyl.

4. A compound according to claim 3 wherein R is methoxy or ethoxy.

5. A compound according to claim 3 wherein R is l-LH.

-6. A compound of formula A according to claim 1 wherein R is hydrogen.

7. A compound according to claim 6 wherein R is alkoxy, and R is methylor ethyl.

8. A compound according to claim 7 wherein R is methoxy or ethoxy. I

9. A compound according to claim 7 wherein R is H,H.

10. A compound of the formula A according to claim.

2. A compound of formula A according to claim 1 wherein R1 is hydrogen.3. A compound according to claim 2 wherein R is alkoxy, and R3 is methylor ethyl.
 4. A compound according to claim 3 wherein R is methoxy orethoxy.
 5. A compound according to claim 3 wherein R2 is H,H.
 6. Acompound of formula A according to claim 1 wherein R3 is hydrogen.
 7. Acompound according to claim 6 wherein R is alkoxy, and R1 is methyl orethyl.
 8. A compound according to claim 7 wherein R is methoxy orethoxy.
 9. A compound according to claim 7 wherein R2 is H,H.
 10. Acompound of the formula A according to claim 1 wherein each of R1 and R3is lower alkyl.
 11. A compound according to claim 10 wherein R isalkoxy.
 12. A compound according to claim 11 wherein R is methoxy orethoxy.
 13. A compound according to claim 11 wherein R2 is H,H.
 14. Acompound of formula B according to claim 1, wherein R1 is methyl orethyl and R'' is alkyl.
 15. A compound of formula C according to claim 1wherein R3 is methyl or ethyl and R'' is alkyl.